Differential distribution of 5HT1D- and 5HT1B-immunoreactivity within the human trigemino-cerebrovascular system: implications for the discovery of new antimigraine drugs.
Sumatriptan, a 5HT1B/1D-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT1B-receptor mediated response). The antimigraine activity of sumatriptan may also result from inhibition of the release of vasoactive neuropeptides from trigeminal sensory fibres within the meninges. The identity of the 5HT1B/1D-receptor subtype mediating this effect is unknown. Using 5HT1D- and 5HT1B-receptor-specific antibodies we have demonstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT1B-receptor protein was detected on dural arteries. In contrast, only 5HT1D-receptor protein was detected on trigeminal sensory neurones including peripheral and central projections to dural blood vessels and to the medulla. Within the medulla 5HT1D-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings have important implications for the design of new antimigraine drugs.
Longmore
J
J
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Shaw
D
D
Smith
D
D
Hopkins
R
R
McAllister
G
G
Pickard
J D
JD
Sirinathsinghji
D J
DJ
Butler
A J
AJ
Hill
R G
RG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001933:Brain Stem / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004388:Dura Mater / Q000098:blood supply; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000737:chemistry*; D012701:Serotonin / Q000032:analysis*; D014276:Trigeminal Nerve / Q000737:chemistry* / Q000166:cytology
D012701:Serotonin